CD4⁺ to CD8⁺ T cell imbalance drives poor Achilles tendon repair in patients

Insufficient healing of the Achilles tendon remains a frequent clinical challenge, creating a need for early markers that identify patients at risk of impaired healing. To examine whether adaptive immunity contributes to these outcomes, we analyzed T cell subsets in blood and hematoma collected during surgery. Patients with a higher CD4⁺/CD8⁺ T cell ratio at surgery reported more pain, showed reduced functional recovery, and greater tendon strain after 12 months. Conversely, elevated CD8⁺ T cell levels, and the CD28-/CD57⁺ memory subset, coincided with more favorable outcomes. We then investigated how these cells affect tendon healing by co-culturing human tenocytes with CD4⁺ or CD8⁺ T cells. Exposure to CD4⁺ T cells increased collagen type 3, IL-17 receptors and matrix metalloproteinases expression, indicating a shift toward impaired extracellular matrix organization. These results suggest that the CD4⁺/CD8⁺ T cell balance may serve as a prognostic marker and that modulating CD4⁺ T cell activity or IL-17 signaling could improve tendon repair.